chr10-70751772-G-A

Variant names:

• chr10-70751772-G-A
• rs12784847
• NM_080722.4:c.2596+126G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080722.4(ADAMTS14):​c.2596+126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,304,004 control chromosomes in the GnomAD database, including 45,098 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (4749 hom., cov: 32)
  • Exomes 𝑓: 0.26 (40349 hom.)
• Consequence: ADAMTS14 NM_080722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940
• Publications: 2 publications found

Genes affected

ADAMTS14 (HGNC:14899): (ADAM metallopeptidase with thrombospondin type 1 motif 14) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme cleaves amino-terminal propeptides from type I procollagen, a necessary step in the formation of collagen fibers. Mutations in this gene may be associated with osteoarthritis in human patients. [provided by RefSeq, May 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080722.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	NM_080722.4	MANE Select	c.2596+126G>A		intron	N/A	NP_542453.2
	ADAMTS14	NM_139155.3		c.2605+126G>A		intron	N/A	NP_631894.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS14	ENST00000373207.2	TSL:1 MANE Select	c.2596+126G>A		intron	N/A	ENSP00000362303.1
	ADAMTS14	ENST00000373208.5	TSL:2	c.2605+126G>A		intron	N/A	ENSP00000362304.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37333 AN: 151998 Hom.: 4752 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.261 AC: 300972 AN: 1151888 Hom.: 40349 AF XY: 0.258 AC XY: 145955 AN XY: 565080

African (AFR) AF: 0.199 AC: 5283 AN: 26546

American (AMR) AF: 0.248 AC: 7078 AN: 28560

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 6749 AN: 19368

East Asian (EAS) AF: 0.195 AC: 6736 AN: 34562

South Asian (SAS) AF: 0.144 AC: 9055 AN: 63086

European-Finnish (FIN) AF: 0.274 AC: 10706 AN: 39012

Middle Eastern (MID) AF: 0.261 AC: 896 AN: 3428

European-Non Finnish (NFE) AF: 0.272 AC: 241399 AN: 888132

Other (OTH) AF: 0.266 AC: 13070 AN: 49194

GnomAD4 genome AF: 0.246 AC: 37354 AN: 152116 Hom.: 4749 Cov.: 32 AF XY: 0.245 AC XY: 18197 AN XY: 74356

African (AFR) AF: 0.199 AC: 8266 AN: 41504

American (AMR) AF: 0.252 AC: 3857 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1155 AN: 3472

East Asian (EAS) AF: 0.210 AC: 1081 AN: 5152

South Asian (SAS) AF: 0.147 AC: 709 AN: 4822

European-Finnish (FIN) AF: 0.278 AC: 2942 AN: 10586

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18552 AN: 67962

Other (OTH) AF: 0.249 AC: 527 AN: 2116

Alfa AF: 0.263 Hom.: 5395

Bravo AF: 0.245

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		-0.094
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12784847; hg19: chr10-72511528; COSMIC: COSV64602536;